Cardiovascular magnetic resonance detects microvascular dysfunction in a mouse model of hypertrophic cardiomyopathy

Journal of Cardiovascular Magnetic Resonance

Yi-Ching Lai¹  Andreas Pohlmann¹  Min-Chi Ku²  Thoralf Niendorf³  Frank Kober⁴  Michael Bader⁵  Lucie Carrier⁶  Fatimunnisa Qadri⁷ 

[1] Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle Strasse 10, 13125, Berlin, Germany;Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle Strasse 10, 13125, Berlin, Germany;DZHK (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany;Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle Strasse 10, 13125, Berlin, Germany;DZHK (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany;Experimental and Clinical Research Center (ECRC), A Joint Cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany;Centre de Résonance Magnétique Biologique et Médicale (CRMBM), Aix-Marseille University, CNRS, Marseille, France;DZHK (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany;Molecular Biology of Peptide Hormones, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany;Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;DZHK (German Centre for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, Berlin, Germany;Molecular Biology of Peptide Hormones, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany;

关键词: Hypertrophic cardiomyopathy (HCM);    Myocardial remodelling;    Microvascular dysfunction;    Perfusion;    Myocardial blood flow (MBF);    Cardiac MRI (CMR);    Arterial spin labelling (ASL);   

DOI  :  10.1186/s12968-021-00754-z

来源: Springer

【 摘 要 】

BackgroundHypertrophic cardiomyopathy (HCM) related myocardial vascular remodelling may lead to the reduction of myocardial blood supply and a subsequent progressive loss of cardiac function. This process has been difficult to observe and thus their connection remains unclear. Here we used non-invasive myocardial blood flow sensitive CMR to show an impairment of resting myocardial perfusion in a mouse model of naturally occurring HCM.MethodsWe used a mouse model (DBA/2 J; D2 mouse strain) that spontaneously carries variants in the two most susceptible HCM genes—Mybpc3 and Myh7 and bears the key features of human HCM. The C57BL/6 J (B6) was used as a reference strain. Mice with either B6 or D2 backgrounds (male: n = 4, female: n = 4) underwent cine-CMR for functional assessment at 9.4 T. Left ventricular (LV) wall thickness was measured in end diastolic phase by cine-CMR. Quantitative myocardial perfusion maps (male: n = 5, female: n = 5 in each group) were acquired from arterial spin labelling (cine ASL-CMR) at rest. Myocardial perfusion values were measured by delineating different regions of interest based on the LV segmentation model in the mid ventricle of the LV myocardium. Directly after the CMR, the mouse hearts were removed for histological assessments to confirm the incidence of myocardial interstitial fibrosis (n = 8 in each group) and small vessel remodelling such as vessel density (n = 6 in each group) and perivascular fibrosis (n = 8 in each group).ResultsLV hypertrophy was more pronounced in D2 than in B6 mice (male: D2 LV wall thickness = 1.3 ± 0.1 mm vs B6 LV wall thickness = 1.0 ± 0.0 mm, p < 0.001; female: D2 LV wall thickness = 1.0 ± 0.1 mm vs B6 LV wall thickness = 0.8 ± 0.1 mm, p < 0.01). The resting global myocardial perfusion (myocardial blood flow; MBF) was lower in D2 than in B6 mice (end-diastole: D2 MBFglobal = 7.5 ± 0.6 vs B6 MBFglobal = 9.3 ± 1.6 ml/g/min, p < 0.05; end-systole: D2 MBFglobal = 6.6 ± 0.8 vs B6 MBFglobal = 8.2 ± 2.6 ml/g/min, p < 0.01). This myocardial microvascular dysfunction was observed and associated with a reduction in regional MBF, mainly in the interventricular septal and inferior areas of the myocardium. Immunofluorescence revealed a lower number of vessel densities in D2 than in B6 (D2 capillary = 31.0 ± 3.8% vs B6 capillary = 40.7 ± 4.6%, p < 0.05). Myocardial collagen volume fraction (CVF) was significantly higher in D2 LV versus B6 LV mice (D2 CVF = 3.7 ± 1.4% vs B6 CVF = 1.7 ± 0.7%, p < 0.01). Furthermore, a higher ratio of perivascular fibrosis (PFR) was found in D2 than in B6 mice (D2 PFR = 2.3 ± 1.0%, B6 PFR = 0.8 ± 0.4%, p < 0.01).ConclusionsOur work describes an imaging marker using cine ASL-CMR with a potential to monitor vascular and myocardial remodelling in HCM.

【 授权许可】

CC BY